Identification of lesions indicating rejection in kidney transplant biopsies: tubulitis is severely under-detected by conventional microscopy

Abstract

Background: In the current international Banff classification of kidney transplant rejection, tubulitis and intimal arteritis are regarded as the key histological features of acute rejection. Grade 1 tubulitis can sometimes be seen in biopsies that do not represent acute rejection; but in the case of intimal arteritis, just one lymphocyte can justify anti-rejection treatment. Our aim was to audit reliability and accuracy of recognizing tubulitis and intimal arteritis using the approach recommended by the Banff classification and correlate any discrepancies with subsequent graft function.

Methods: This is a retrospective review of all kidney transplant biopsies reported as negative for rejection from 1 January 2009 to 31 December 2009 to assess the presence or absence of occult tubulitis and arteritis. Lymphocytes were immunostained with CD3, using Periodic Acid Schiff as a counterstain. Sections were reviewed to detect missed intimal arteritis and tubulitis. Discrepancies between the report and the immunostain results were analysed by biopsy type and broken down by the reporting pathologist. The graft function of any patient with missed lesions was checked to test for adverse impact on the patient.

Results: 'Missed' tubulitis was found in 68% of biopsies, but only two such cases subsequently developed biopsy-proven acute rejection. Only one case of missed intimal arteritis was found (1%) and the subsequent clinical course suggested that this was probably early rejection. There was no significant difference between the reporting pathologists.

Conclusions: We conclude that tubulitis is missed very frequently, but the Banff classification seems to be 'calibrated' to allow for this and it does not seriously affect the identification of clinically significant acute rejection. Immunostaining is therefore not indicated in routine practice because (by Banff criteria) it would result in over-diagnosis of rejection. Intimal arteritis can indicate acute rejection even if extremely mild.